Development and Characterization of Novel Chitosan-Coated Curcumin Nanophytosomes for Treating Drug-Resistant Malaria.

ABSTRACT

This study aimed at enhancing the efficacy of curcumin (CR) by formulating and coating it with chitosan. In silico molecular docking studies revealed that CR exhibited almost similar and low binding energies when compared to artemisinin, indicating high stability at the target site. It can be confirmed that CR is effective in treating and reducing Plasmodium falciparum parasites. Fourier transform infrared studies confirmed that there was a shift and disappearance of some drug peaks in the formulation which revealed complexation with phospholipids. The F2EXT3-developed formulation exhibited greater solubility (24.31 ± 3.47 µg/mL) when compared to pure CR (7.99 ± 1.95 µg/mL). Proton nuclear magnetic resonance studies confirmed the formation of Curcumin-phospholipid hydrogen bonding in F2EXT3. The in vitro drug release studies revealed that the developed formulation F2EXT3 exhibited better drug release at 71.98% at 48 h; this might be due to the effective entrapment efficiency of the drug inside the phospholipid, presence of polyethylene glycol 4000 and chitosan further assisted in sustained release of the drug. Scanning electron microscopy studies revealed that optimized F2EXT3 CR nanophytosomes were nearly spherical with narrow size distribution and smooth surface. The zeta potential of the F2EXT3 showed -3.5 mV. Stability studies revealed that the formulation remained stable even after 6 months. It was observed from the hemin assay that CR and F2EXT3 exhibited (50 µg/mL curcumin) exhibited IC50 values of 47 ± 2.45 and 22 ± 1.58 µM, respectively. Further in vivo antimalarial activity on resistant and sensitive strains needs to be performed to evaluate the efficacy of the developed formulation.